This study is conducted to assess the safety, tolerability and preliminary efficacy of AST2818 in patients with advanced Non Small Cell Lung Cancer (NSCLC).
Name: Alflutinib
Description: patients take Alflutinib orally once per day at different doseType: DrugAlflutinib
Description: Evaluation of objective response rate assessed by RECIST 1.1
Measure: Objective response rate of Alflutinib Time: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, whichever came first, assessed up to 52 weeks.Description: Duration of response assessed by RECIST 1.1
Measure: Duration of response of Alflutinib Time: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, whichever came first, assessed up to 52 weeks.Description: Progression of tumor was assessed by RECIST 1.1 thereby to evaluate progression free survival
Measure: Progression free survival of Alflutinib Time: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, whichever came first, assessed up to 52 weeks.Description: Clinical benefit rate was calculated by adding up complete remission, partial remission and stabilization of disease assessed by RECIST 1.1
Measure: Clinical benefit rate of Alflutinib Time: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, whichever came first, assessed up to 52 weeks.Description: Progression of tumor was assessed by RECIST 1.1 thereby to evaluate disease control rate
Measure: Disease control rate of Alflutinib Time: CT or MRI at screening and every 2 Cycles (from first dose of multiple dosing) until disease progression or withdrawal from study, whichever came first, assessed up to 52 weeks.Description: Assessed by number and severity of adverse events as recorded on the case report form, vital signs, laboratory variables, physical examination, electrocardiogram, ophthalmic examinations, RECIST1.1, and NCI CTCAE v4.03
Measure: Incidence and Severity of Treatment-Emergent Adverse Events Time: Adverse events will be collected from baseline until 28 days after the last doseDescription: Cmax of Alflutinib and 2 metabolites at steady state following multiple doses
Measure: Steady state Maximum Plasma Concentration [Cmax] of multiple doses Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Description: tmax of Alflutinib and 2 metabolites at steady state following multiple doses.
Measure: Steady state peak plasma time [tmax] of multiple doses Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Description: Cmin of Alflutinib and 2 metabolites at steady state following multiple doses.
Measure: Steady state Cmin (Minimum Plasma Concentration) of multiple doses Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Description: AUC of Alflutinib and 2 metabolites at steady state following multiple doses.
Measure: Steady state area under the plasma concentration versus time curve [AUC] of multiple doses Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Description: Clearance of Alflutinib and 2 metabolites at steady state following multiple doses.
Measure: Steady state clearance of multiple doses Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Description: Accumulation ratio of Alflutinib and 2 metabolites following multiple doses.
Measure: Accumulation ratio of multiple doses Alflutinib and 2 metabolites Time: Blood samples will be collected from each subject at pre-specified times during the multiple dosing cycles (Cycle 1-pre-dose Day 1, 8, 15. Cycle 2 D1- pre-dose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 48, 72 hours post dose)Single Group Assignment
There are 2 SNPs
- Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including at least one of G719X, exon 19 deletion, L858R, L861Q mutation) - Documented evidence of definitely EGFR T790M+ state in the tumor tissue after disease progression on the most recent treatment regimen (irrespective of whether this is EGFR TKI or chemotherapy). --- L858R ---
- Confirmation that the tumour harbours an EGFR mutation known to be associated with EGFR TKI sensitivity (including at least one of G719X, exon 19 deletion, L858R, L861Q mutation) - Documented evidence of definitely EGFR T790M+ state in the tumor tissue after disease progression on the most recent treatment regimen (irrespective of whether this is EGFR TKI or chemotherapy). --- L858R --- --- L861Q ---